Animals ; Betaine-Homocysteine S-Methyltransferase ; therapeutic use ; Homocysteine ; blood ; Hyperhomocysteinemia ; blood ; therapy ; Male ; Rats ; Rats, Wistar ; Recombinant Proteins ; therapeutic use

Gambogic acid-loaded polylacticacid nanoparticles (GA-PLA-NPs) were prepared by modified emulsification solvent diffusion. The shape of nanoparticles was observed by transmission electron microscope (TEM).The size distribution and mean diameter were measured by laser particle size analyzer. The entrapment efficiency and content of drug loading were determined by Ultraviolet Spectrophotometer after ultracentrifugation. GA-PLA-NPs release behavior in vitro was carried out. The acute toxicity were carried out to study the security of GA-PLA-NPs. The preparation process adapted to the formulation was as follows: the volume ratio of the aqueous and organic was 2∶1(v/v), the surfactant concentration in aqueous was 0.5%,the drug concentration in organic was 0.1%(w/v), GA∶PLA was 1∶4(w/w). The mean diameter was 51.36nm for the nanoparticles prepared by above conditions.The entrapment efficiency and content of drug loading were 98.87 % and 13.3 %. The release behavior of drug in vitro showed an initial burst effect with subsequently a slower rate stage. The LD50 value of GA-PLA-NPs on mouse was 26.3 mg/kg. The results showed that the GA-PLA-NPs were well prepared with stable quality and high dispersion. PLA-NPs might be used as a new carrier for gambogic acid.

Objective: To study the effect of wortmannin (WM), a PI3K/Akt inhibitor, on the proliferation and apoptosis of leukemia cells and the possible mechanism. Methods: Human leukemia cell line K562 was treated with different concentrations of WM. The proliferation of K562 cells was examined by MTT assay. DNA damage in K562 cells was examined by single cell gel electrophoresis assay, and apoptosis of K562 cells was detected by Annexin V-FITC/PI double-staining. The expressions of total Akt, phosphorate-Akt (p-Akt), and NF-κB p65 mRNA and protein were detected by RT-PCR and Western blotting, respectively. Results: WM inhibited the proliferation of K562 cells in a dose- and time-dependent manner, with the IC((50) value of 24 h being 25 nmol/L. WM also induced apoptosis of K562 cells in a dose-dependent manner. DNA damage in K562 cells was demonstrated by appearance of comet tail after treatment with WM, with the rate of DNA tail and the tail length being significantly higher than those in the control group (P<0.01). WM dose-dependently inhibited P-Akt and NF-κB p65, but not the total Akt, mRNA and protein expressions. Conclusion: WM can inhibit proliferation and induce apoptosis of K562 cells in a dose- and time-dependent manner, probably through down-regulation of phosphorate PI3K/Akt signal pathway and NF-κB expression.

Animals ; Apoptosis ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cells, Cultured ; HSP70 Heat-Shock Proteins ; metabolism ; Heat Stress Disorders ; metabolism ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar

Animals ; Cognition ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Electrocardiography ; Female ; Heart ; drug effects ; physiopathology ; Male ; Mice ; Mice, Inbred Strains ; Myocardium ; pathology ; Phytotherapy ; methods

Overexpression of human ether-脿-go-go (eag) related gene (hERG) has been found in a broad range of human leukemia cell lines and primary human leukemia. The block of hERG protein might be a potential therapeutic strategy for leukemia. Gambogic acid (GA) has recently exhibited marked anti-tumor potency on solid tumors of various derivations. Here, we investigated the anti-leukemia effects of GA and its relation to the regulation of hERG in K562 leukemia cells in vitro. K562 cells were treated with various concentrations of GA (0.125-8.0 micromol/L) for 0-72 h. MTT assay was used to evaluate the inhibition effect of GA on the growth of K562 cells. Cell apoptosis was measured through both Annexin-V FITC/PI double-labeled cytometry and transmission electron microscopy. Cell cycle regulation was studied by a propidium iodide method. RT-PCR and Western blot were applied to detect the expression level of hERG in K562 cells. GA presented striking growth inhibition and apoptosis induction potency on K562 cells in vitro in a time- and dose-dependent manner. The IC(50) value of GA for 24 h was 2.637+/-0.208 micromol/L. Moreover, GA induced K562 cells arrested in G(0)/G(1) phase, accordingly, cells in S phase decreased gradually, and no obvious changes were found in G(2)/M phase cells. Under the transmission electron microscopy, apoptotic bodies containing nuclear fragments were found in GA-treated K562 cells. After treatment with GA of 2.0 micromol/L for 24 h, the percentage of apoptotic cells was increased from 4.09% to 18.47% (P<0.01). Overexpression of hERG channel was found in K562 cells, while GA could down-regulate it at both protein and mRNA levels (P<0.01). It was concluded that GA exhibited its anti-leukemia effects partially through down-regulating the expression level of hERG channel in K562 cells, suggesting that GA may be a potential agent against leukemia with a mechanism of blocking hERG channel.

Objective To evaluate the value of ultrasound elastography score and strain ratio index in the differential diagnosis of thyroid solid nodules. Methods Eighty-six thyroid solid nodules of 69 patients were divided into 2 groups based on their pathologic results: benign nodules group and malignant nodules group.Compared with pathological results, each thyroid solid nodules' elastographic scores and strain ratio index were respectively analyzed. The sensitivity, specificity and accuracy of elasticity score and strain ratio index were calctlated.The receiver operator characteristic (ROC) curves were drawn according to the results, to choose the best cut-off value.Results There were 67 nodules in benign nodules group and 19 nodules in malignant nodules group. The diameter of benign nodules was (2.05 ± 0.21)cm, malignant nodules was (1.62 ± 0.12)cm. There were no significant differences in the elasticity score and strain ratio index between benign and malignant nodules(t= - 1.736, P ＞ 0.05). Malignant lesions had a higher score and strain ratio index(median 3, 3.97, respectively) than benign ones(median 2, 1.66,respectively, Z = - 5.290, - 5.450, all P ＜ 0.05). If the cut-off value of the elastographic scores was equal or more than 3, the sensitivity, specificity and accuracy were 84.2%(16/19) ,86.6%(58/67) and 86.0%(74/86), respectively,with an area under ROC curve of 0.854. If the cut-off value of the strain ratio index was equal or more than 2.50,the sensitivity, specificity and accuracy were 89.4%(17/19),86.6%(58/67) and 87.2%(75/86), respectively, with an area under ROC curve of 0.911. Conclusion Elasticity score and strain ratio index are helpful in differentiating benign and malignant lesions of thyroid with high clinical value.

Backgroud and Objective Proline-rich tyrosine kinase2(Pyk2) is a Ca~(2+) sensitive,non-receptor tyrosine protein kinase.Previous reports showed Pyk2 involved in development of left ventrieular hypertrophy. The present paper aimed to study the effects of valsartan on ventricular hypertrophy and its effect on the expression of Pyk2 in myocardium in renovascular hypertensive rats(RHR).Methods Two-kidney and one-clip(2K1C) renal hypertensive model was established in Sprague-Dawley rats by chronic partial occlusion of left renal artery,and ran- domized to receive valsartan (30 mg/kg?d) or without treatment for 4 or 8 weeks.Left ventricular mass to body mass ratio was measured.Pyk2 protein expression and phosphorylation was detected by Western blotting.Results Blood pressure,left ventricular mass to body mass ratio,Pyk2 activity in myocardium of RHR were increased gradu- ally.Valsartan reduced BP and prevent myocardial hypertrophy(P

Objective To investigate the correlation of hepatitis B patients in Fuzhou between resistance patterns in HBV P region and genotype,HBeAg,the hepatitis B process.Methods This was a retrospective study.The serum and clinic data of 1 115 hepatitis B patients were collected from the inpatient and outpatient Center for Liver Diseases in First Affiliated Hospital of Fujian Medical University between October 2011 and January 2015.HBV DNA was extracted and sequenced using the Sanger method to detect HBV genotype and resistance mutations in P region,HBeAg and HBeAb concentration were detected by chemiluminescent assay.The relationship between P region resistance mutations pattern,HBV genotype,serum HBeAg and the hepatitis B process was analyzed.The x2-test was used to compare the resistance rate and positive rate.Results There were significant differences between 14 kinds of resistance loci and the genotype distribution(x2 =30.788,P =0.004),the C/B genotype ratio of three common resistance loci (rtM204V/I,rtL180M,rtA181T/V) were 85/82,49/25 and 27/9,respectively,which in genotype C was higher than genotype B.The resistance ratio of hepatocellular carcinoma,liver cirrhosis,chronic hepatitis B,hepatitis B carriers was 31.4％ (11/35),37.6％ (65/173),27.3％ (146/535) and 21.8％ (43/197),respectively,which showed significant difference between the four clinical diagnosis (x2 =11.858,P =0.008).The highest percentage of resistance was liver cirrhosis,followed by hepatocellular carcinoma and chronic hepatitis B.There was significant difference in the distribution of HBV genotype between HBeAg (+) group and HBeAg (-) group (x2 =11.093,P =0.001),the HBeAg positive rate in genotype C [37.53％ (295/786)] was higher than in genotype B[35.62％ (280/786)].However,the total resistance rate between HBeAg (+) group and HBeAg(-) group was not significantly different[23.7％ (136/573) and 24.6％ (52/211),respectively,x2 =0.07,P =0.791].Conclusions HBV genotype was related to the resistance rates,HBeAg levels and the progress of hepatitis B.The resistance rate and HBeAg positive rate of genotype C were higher than those of genotype B,and clinical outcomes were worse in genotype C.HBV resistance rates and HBeAg levels were related to the progress of hepatitis B,the higher the resistance rates,the worse clinical outcomes.

Adult ; Behcet Syndrome ; complications ; Female ; Heart Atria ; pathology ; Humans ; Myocardial Infarction ; complications ; Pericardial Effusion ; complications